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Biomedical subjects

Qing Ye

Publications and source records attributed to Qing Ye.

At least 37 records · Page 2Linked to original sources
PubMed2005

BRAF mutation predicts sensitivity to MEK inhibition.

The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS and RAF family members. Using small-molecule inhibitors of MEK and an integrated genetic and pharmacologic analysis, we find that mutation of BRAF is associated with enhanced and selective sensitivity to MEK inhibition when compared to either 'wild-type' cells or cells harbouring a RAS mutation. This MEK dependency was observed in BRAF mutant cells regardless of tissue lineage, and correlated with both downregulation of cyclin D1 protein expression and the induction of G1 arrest. Pharmacological MEK inhibition completely abrogated tumour growth in BRAF mutant xenografts, whereas RAS mutant tumours were only partially inhibited. These data suggest an exquisite dependency on MEK activity in BRAF mutant tumours, and offer a rational therapeutic strategy for this genetically defined tumour subtype.

Animals↗
PubMed2005

Combined electric and acoustic stimulation of the auditory system: results of a clinical study.

Combined electric and acoustic stimulation (EAS) of the auditory system is a new therapy for patients with severe to profound high- and mid-frequency hearing loss but remaining low-frequency hearing. In a prospective study, 13 patients with low-frequency hearing of better than 60 dB below 1 kHz were implanted with a MED-EL COMBI 40+ cochlear implant. Pure tone thresholds as well as monosyllabic word scores and Hochmair-Schulz-Moser sentences in quiet and in noise were measured with hearing aids, cochlear implant alone and in the combined stimulation mode (EAS) in the same ear. Hearing could be partially preserved in 11 out of the 13 patients. All patients scored significantly higher with cochlear implant alone than with hearing aids. Seven patients scored higher in the EAS mode than with cochlear implant alone for sentences in noise, 4 remained unchanged, and 2 could not use EAS. Synergistic effects of EAS were most prominent for hearing in noise with increases of up to 72% as compared to cochlear implant alone.

Acoustic Stimulation↗
PubMed2005

Time to remission and relapse after the first hospital admission in severe bipolar disorder.

BACKGROUND: Few studies of the time to remission and first relapse in severe bipolar disorder have been based on epidemiologically defined samples or have examined patient characteristics and time-varying indicators of medication use simultaneously. Using a cohort from the Suffolk County Mental Health Project, we describe these temporal patterns and their relationships with childhood, illness, and treatment characteristics. METHOD: A multi-facility cohort of 123 first-admission inpatients with DSM-IV bipolar disorder with psychotic features was followed for 4 years. Dates of the first complete remission (lasting at least 2 months), subsequent relapses, and use of antimanic (AM),antipsychotic (AP), and antidepressant (AD) medications were recorded. Childhood and illness characteristics were ascertained at baseline using standard instruments. RESULTS: By the 4-year point, 83.7% had achieved a full remission, with 42.3% remitting within 3 months, 63.4% within 6 months, and 74.8% within 1 year. Overall, younger age of onset, history of childhood psychopathology, and higher Brief Psychiatric Rating Scale (BPRS) anxiety/depression scores were significantly associated with longer time to remission. Discontinuing AM, AP and AD (compared to never using) and taking AP and AD (compared to never using) were significantly associated with remission in the multivariate analysis. Of the 103 participants with complete remission, 61.2% suffered a relapse; 24.3 % relapsed within 6 months of remission, and 35.9% within a year. Overall, 32.5% of the 123 participants had a single episode followed by full remission. Childhood internalizing-type problems, higher BPRS anxiety/depression and Hamilton depression scores, and an admission episode not involving mania, but not patterns of medication use, were associated with shorter time to relapse. CONCLUSION: By 4-year follow-up, the majority of severely ill bipolar patients had remitted from their initial episode, but more than half subsequently relapsed. Illness characteristics, especially depressive symptoms, and medication treatment were associated with the early course, although medication use after remission was not associated with relapse.

Adult↗
PubMed2005

The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells.

Tumor cells with mutated PTEN proliferate in an EGFR-independent manner. Induction of PTEN sensitizes cells to EGFR inhibition, and the combination causes synergistic apoptosis. Synergy is due to inhibition of two parallel pathways that phosphorylate the proapoptotic protein BAD at distinct sites. Serine 112 phosphorylation is EGFR/MEK/MAPK dependent, whereas serine 136 phosphorylation is PI3K/Akt dependent. Either phosphorylation is sufficient to sequester BAD to 14-3-3. BAD is released and apoptosis is induced only if both serines are dephosphorylated in response to inhibition of both pathways. Reduction of BAD expression by RNA interference prevents apoptosis in response to pathway inhibition. Thus, BAD integrates the antiapoptotic effects of both pathways. Combined inhibition of EGFR and PI3K signaling may be a useful therapeutic strategy.

Animals↗
PubMed2004

Transforming growth factor-beta down-regulates apolipoprotein M in HepG2 cells.

Apolipoprotein M (apoM) is a novel apolipoprotein presented mostly in high-density lipoprotein (HDL) in human plasma, and is exclusively expressed in liver and in kidney. The pathophysiological function of apoM has not yet been elucidated. Apolipoprotein B (apoB), the characteristic apolipoprotein of low-density lipoprotein (LDL), is like apoM, a very hydrophobic protein, and thereafter they both must co-circulate with lipoprotein particles in plasma. The cytokine, transforming growth factor-beta (TGF-beta), has been shown to decreased apoB secretion in HepG2 cells, and we hypothesized that TGF-beta may have the same effects on apoM expression in HepG2 cells. In the present study, we used real-time RT-PCR to analyze apoM and apoB mRNA levels during administration of TGF-beta, as well as TGF-alpha, epidermal growth factor (EGF) and hepatic growth factor (HGF). TGF-beta significantly inhibited both apoM and apoB mRNA expression in HepG2 cells. The inhibitory effects of TGF-beta were dose-dependent, i.e. 1 ng/ml of TGF-beta decreased apoM mRNA levels by 30%, and 10 or 100 ng/ml of TGF-beta decreased apoM mRNA levels more than 65%. The effect of TGF-beta on apoB mRNA expression was slightly weaker than that of apoM, with a maximum effect at 10 or 100 ng/ml TGF-beta where apoB mRNA levels decreased about 55%. The inhibitory effects of TGF-beta on apoM and apoB mRNA levels also increased with increasing incubation time, where the maximum effect was obtained at 24 h. Moreover TGF-alpha, EGF and HGF all decreased both apoM and apoB mRNA levels, but to a less extent than TGF-beta. Further, all four cytokines had more pronounced effects on apoM mRNA expression than apoB mRNA expression. The present study suggested that apoM, like apoB, may be involved in the hepatic lipoprotein assembly in vivo.

Apolipoproteins↗
PubMed2004

Expression pattern of apolipoprotein M during mouse and human embryogenesis.

Apolipoprotein M (apoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL), and in minor proportions in triglyceride-rich lipoprotein (TGRLP) and low-density lipoprotein (LDL). The gene encoding apoM is present in all mammalian genomes. The identity of the apoM gene of human, rat and mouse is over 80%. However, the (patho)physiological functions of apoM are unknown yet. In the present study, we investigated apoM expression patterns during mouse and human embryogenesis. ApoM transcripts were detectable in mouse embryos from day 7.5 to day 18.5. ApoM was expressed at low levels at day 7.5, its expression increased significantly at day 9.7, decreased at day 10.5, and then increased continually up to day 18.5. ApoM-positive cells appeared mainly in liver of day-12 embryos as detected by in situ hybridization. In day-15 embryos, apoM was expressed in both liver and kidney. During human embryogenesis, apoM was mainly expressed in liver and kidney and little was found in small intestine as determined by mRNA array of human fetal normal tissues. ApoM was also detected in stomach and skeletal muscle in early stages of embryogenesis (3-5 months).

Animals↗
PubMed2004

A novel pattern of pp65-positive cytomegalic endothelial cells circulating in peripheral blood from a renal transplant recipient.

The present study reports a novel pattern of cytomegalic endothelial cells (CEC) in peripheral blood from a female renal transplant recipient infected with human cytomegalovirus (HCMV), which has not been reported previously. Localization of specific early antigen of HCMV, pp65 antigen, was examined by immunohistochemistry. Staining of an endothelial cell marker (CD34) was used to characterize endothelial cells. It is demonstrated that many leukocytes surrounded and adhered to a protein-like material, in which pp65-positive CEC were detected. The composition and function of this protein-like material are yet unknown. The patient lacked clinical symptoms of HCMV disease. Furthermore, similar localization patterns were found in other renal transplant recipients suffering from HCMV infections as determined by real-time PCR to detect HCMV DNA in blood. These patients showed no or only minor clinical symptoms of HCMV infection. It is suggested that these novel localization patterns of CEC may play a role in the host defense in patients infected with HCMV, but the exact relation between HCMV infection and CEC formation needs further investigation.

Cytomegalovirus↗
PubMed2004

Conservation of low-frequency hearing in cochlear implantation.

OBJECTIVES: As results with cochlear implants have continued to improve, patients with some remaining cochlear function have become eligible for cochlear implantation. Thus, preservation of acoustic hearing after implantation has gained importance. Hearing preservation can be considered a benchmark for atraumatic implantation preventing neural degeneration from loss of residual hair cells or subsequent to local trauma. In this prospective study, the possibility of preserving low-frequency hearing in cochlear implantation using a modified surgical technique has been explored. MATERIAL AND METHODS: In a prospective study design, 14 subjects with considerable low-frequency hearing of 20-60 dB in the frequency range 125-500 Hz but with unsatisfactory speech understanding with hearing aids of < 35% monosyllabic word understanding were implanted with a MED-EL COMBI-40+ cochlear implant. The insertion depth was intentionally limited to 19-24 mm to prevent damage to low-frequency regions of the cochlea. Pre- and postoperative pure-tone thresholds were measured. RESULTS: Hearing was conserved within 0-10 dB in 9/14 subjects and within 11-20 dB in 3/14; in 2/14 subjects hearing was completely lost in the implanted ear. Thus hearing could at least partially be conserved in 12/14 subjects (86%). Median threshold values decreased by 10, 15, 17.5 and 5 dB at 125, 250, 500 and 1000 Hz, respectively. Even high levels of hearing, e.g. 30 dB at 500 Hz, could be maintained after implantation in some subjects. CONCLUSIONS: This study reports successful conservation of hearing after cochlear implantation using a modified surgical technique. Even high levels of hearing could be maintained, showing that implantation of an intracochlear electrode can be performed atraumatically with preservation of functional structures.

Adult↗
PubMed2004

A cohesion/tension mechanism explains the gating of water channels (aquaporins) in Chara internodes by high concentration.

Isolated internodes of Chara corallina have been used to study the gating of aquaporins (water channels) in the presence of high concentrations of osmotic solutes of different size (molecular weight). Osmolytes were acetone and three glycol ethers: ethylene glycol monomethyl ether (EGMME), diethylene glycol monomethyl ether (DEGMME), and triethylene glycol monoethyl ether (TEGMEE). The 'osmotic efficiency' of osmolytes was quite different. Their reflection coefficients ranged between 0.15 (acetone), 0.59 (EGMME), 0.78 (DEGMME), and 0.80 (TEGMEE). Bulk water permeability (Lp) and diffusive permeabilities (Ps) of heavy water (HDO), hydrogen peroxide (H2O2), acetone, and glycol ethers (EGMME, DEGMME, and TEGMEE) were measured using a cell pressure probe. Cells were treated with different concentrations of osmotic solutes of up to 800 mM ( approximately 2.0 MPa of osmotic pressure). Inhibition of aquaporin activity increased with both increasing concentration and size of solutes (reflection coefficients). As cell Lp decreased, Ps increased, indicating that water and solutes used different passages across the plasma membrane. Similar to earlier findings of an osmotic gating of ion channels, a cohesion/tension model of the gating of water channels in Chara internodes by high concentration is proposed. According to the model, tensions (negative pressures) within water channels affected the open/closed state by changing the free energy between states and favoured a distorted/collapsed rather than the open state. They should have differed depending on the concentration and size of solutes that are more or less excluded from aquaporins. The bigger the solute, the lower was the concentration required to induce a reversible closure of aquaporins, as predicted by the model.

Acetone↗
PubMed2004

Application of carbon dioxide and erbium:yttrium-aluminum-garnet lasers in inner ear surgery: an experimental study.

BACKGROUND: Surgery of the inner ear requires atraumatic techniques to preserve the sensory structures of the inner ear. With modern laser technology, surgery can be performed without mechanical contact, reducing the risk of direct mechanical trauma. However, energy transfer by laser light has the potential to induce damage by heating, pressure waves, or direct irradiation, depending on the properties of the laser and parameters of application. HYPOTHESIS: The application of laser systems in inner ear surgery may have an advantage over traditional techniques; the carbon dioxide laser in continuous mode with an automated scanning procedure and the erbium:yttrium-aluminum-garnet laser were compared with a mechanical technique, using a diamond drill. METHODS: A cochleostomy in the basal cochlear turn of guinea pigs was created. Thresholds in response to frequency-specific stimuli and clicks were established by recording compound action potentials, both before and after the procedure. RESULTS: The best results in terms of preservation of cochlear function were obtained with the diamond drill. However, a single ear had a complete loss after fracture of the cochlear wall. Mean threshold shifts observed with the carbon dioxide laser were slightly greater, showing mild high-frequency losses, although differences to the group of drilling were not statistically significant. Results with the erbium:yttrium-aluminum-garnet laser showed significantly higher degrees of hearing loss than the other two groups, predominantly in the high-frequency region. CONCLUSIONS: Mechanical opening of the inner ear using a microdrill can be performed with minimal hearing loss; however, it carries the risk of direct trauma to the inner ear. The carbon dioxide laser with a new scanning technology as a noncontact procedure is shown to be effective and safe. It can be regarded as a useful tool in inner ear surgery. The erbium:yttrium-aluminum-garnet laser has a greater potential to cause damage.

Aluminum↗
PubMed2004

Normal and transplanted rat kidneys: diffusion MR imaging at 7 T.

PURPOSE: To investigate the feasibility of obtaining reproducible apparent diffusion coefficient (ADC) maps of normal rat kidneys by using respiratory-triggered spin-echo diffusion-weighted magnetic resonance (MR) imaging, to investigate the sensitivity of ADC maps in the evaluation of renal blood flow, and to use this technique to monitor acute graft rejection in transplanted rat kidneys. MATERIALS AND METHODS: Spin-echo diffusion-weighted MR imaging measurements were performed in 20 normal rats and nine rats that had undergone transplantation (six rats had received allografts; three had received isografts) at 7 T. To evaluate the effect of alteration in blood flow and water transport function, angiotensin II was infused in six normal rats and a series of spin-echo diffusion-weighted MR images was obtained at five time points. Transplanted kidneys were monitored by obtaining spin-echo diffusion-weighted MR images and gradient-echo MR images every 2 hours for 8 hours on postoperative day 4. Statistical analysis was performed with repeated-measures multivariate analysis of variance and the paired t test. RESULTS: No significant differences in ADC values were observed between right and left kidneys in all three orthogonal directions; however, a small difference was observed between the cortex and medulla. ADC values in the cephalocaudal and mediolateral directions were higher than those in the anteroposterior direction (P <.01 for all). ADC values in the cortex and medulla decreased significantly (by >35%, P <.01) during angiotensin II-induced reduction in renal blood flow. No significant signal intensity change was observed between native and transplanted kidneys on gradient-echo MR images. Allografts exhibited decreased ADC values (P <.01) and isografts exhibited similar ADC values compared with native kidneys. CONCLUSION: These findings suggest that reproducible renal ADC maps can be obtained in rats by using spin-echo diffusion-weighted MR imaging at 7 T. Spin-echo diffusion-weighted MR imaging may have potential as a noninvasive tool for monitoring early graft rejection after kidney transplantation.

Angiotensin II↗
PubMed2004

[Cephlometric analysis of the cranial base in class II(1) malocclusions with different vertical types in adolescences].

PURPOSE: To explore the morphology of the cranial base in Class II(1) malocclusions with different vertical types in adolescence. METHODS: The sample of 60 males and 60 females were divided into Class II(1) high-angle group, average-angle group, and low-angle group and normal occlusion group. Each group had 30 cases. Cephalograms were analyzed for all subjects. Data were obtained to have analysis of variance and LSD multiple range test. RESULTS: The cranial floor base angle (Ba-SE-FMS) of three groups with class II(1) malocclusion was increased. The anterior cranial floor angle was more open in the high angle group, and the flexure of the middle cranial floor was increased in the low angle and average angle groups. The 'effective vertical growth' of cranial floor was decreased while the mandibular plane angle was increased. CONCLUSION: The cranial floor base angle(Ba-SE-FMS) was suitable to describe the flexure of the cranial base, and indicated the mechanism of the Class II(1) malocclusion with different vertical types in adolescence.

Cephalometry↗
PubMed2003

Synthesis and structure-activity relationship of 2-amino-3-heteroaryl-quinoxalines as non-peptide, small-molecule antagonists for interleukin-8 receptor.

Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis.

Anti-Inflammatory Agents↗
PubMed2003

Improving spatiotemporal resolution of USPIO-enhanced dynamic imaging of rat kidneys.

This paper addresses the problem of enhancing spatiotemporal resolution of ultra-small superparamagnetic iron oxide (USPIO)-enhanced dynamic MRI of rat kidneys. To alleviate the limited resolution problem of conventional full-scan Fourier imaging methods, we use a generalized series-based imaging scheme to reduce coverage of kappa-space. Experimental results demonstrate that the generalized series imaging method with basis functions constructed using two references (pre- and post-contrast) can reduce the number of phase encodings measured during the dynamic contrast wash-in process by a factor of 4 with a negligible or minimal loss of image quality. The method is expected to make 3D studies possible using USPIO-enhanced dynamic imaging of rat kidneys, and prove valuable for early detection of renal rejection after kidney transplantation.

Animals↗
PubMed2003

Specific tissue expression and cellular localization of human apolipoprotein M as determined by in situ hybridization.

Apolipoprotein M (apoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL), and in minor proportion in triglyceride-rich lipoprotein (TGRLP) and low-density lipoprotein (LDL). The gene coding for apoM has been detected in all mammal genomes. The function of apoM is unknown yet. In the present study, we demonstrated that apoM is exclusively expressed in a strong manner in adult liver and kidney, and is expressed weakly in fetal liver and kidney as detected with human multiple tissue expression array. Both immunohistochemical staining and apoM mRNA in situ hybridization demonstrated that apoM was exclusively expressed in hepatocytes in human liver and in tubular epithelial cells in human kidney. The present study helps to elucidate the pathophysiological functions of apoM in vivo.

Apolipoproteins↗
PubMed2003

[Expression and characterization of Kringle 1-4.5 domains of human plasminogen].

The cDNA encoding Kringle 1-4 and part of Kringle 5 domains of human plasminogen (K1-4.5), obtained from HepG2 by RT-PCR, was cloned into expression vector pHIL-S1. The recombinant plasmid pHIL-K1-4.5 was transformed into Pichi pastoris GS115 and the recombinant yeast was induced to express the recombinant proteins by methanol. The expressed proteins were purified by lysine affinity chromatography to a purity of 95%. The recombinant K1-4.5 inhibited the growth of bovine capillary endothelial cells (BAEC) stimulated by the basic fibroblast growth factor (bFGF), in a dosage-dependent manner with a half maximal concentration of 2 mg/L. rhK1-4.5 also inhibited 40% of the BAEC migration stimulated by bFGF in the concentration of 1 mg/L.

Animals↗
PubMed2003

[The expression of CD44 and it's significance in human laryngeal carcinoma].

OBJECTIVE: To explore the CD44 expression in different laryngeal carcinoma tissues and their clinical significance. METHOD: Using immunohistochemistry methods to study 261 cases of archived paraffin-embedded laryngeal tissue. RESULT: The results turned out to be as follows: 1. A high level of CD44 expression was more frequently found in laryngeal carcinoma than in precarcinoma lesions and normal tissues. 2. CD44 expression correlated well with histological grades, the higher grade the lower the CD44 expression. 3. The third and fourth stages laryngeal carcinoma had stronger CD44 positive than those of the first and second stages. 4. CD44 expression in laryngeal carcinoma with cervical metastasis were higher than those without cervical metastasis. 5. To 3 and 5 years survival, CD44 positive cases had lower chance than CD44 negative cases. CONCLUSION: These results implicates that the occurrence, development and prognosis of laryngeal carcinoma may be closely related to CD44 expression.

Adult↗